The effects of low‐intensity pulsed ultrasound upon diabetic fracture healing

Coords, Michael; Breitbart, Eric A.; Paglia, David N.; Kappy, Nikolas; Gandhi, Ankur; Cottrell, Jessica; Cedeno, Natalie; Pounder, Neill M.; O’Connor, J. P.; Lin, Sheldon S.

doi:10.1002/jor.21223

Cited by 51 publications

(42 citation statements)

References 46 publications

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“…Diabetic rats with optimal glycemic control did not experience these changes, and the mechanical properties of the bone were similar to non-diabetic animals [23] . Poorly controlled DM also decreases important cytokine production and reduces new blood vessel formation at the site of callus [24] .…”

Section: General Issuesmentioning

confidence: 99%

Diabetes and its negative impact on outcomes in orthopaedic surgery

Wukich

2015

WJO

115

103

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An estimated 285 million adults (aged 20-79 years) worldwide were diagnosed to have diabetes mellitus (DM) in 2010, and this number is projected to grow to 439 million adults by the year 2030. Orthopaedic surgeons, regardless of their subspecialty interest, will encounter patients with DM during their career since this epidemic involves both developed and emerging countries. Diabetes results in complications affecting multiple organ systems, potentially resulting in adverse outcomes after orthopaedic surgery. The purpose of this review is to discuss the pathophysiology of DM and its potential for impacting orthopaedic surgery patients. Diabetes adversely affects the outcome of all orthopaedic surgery subspecialties including foot and ankle, upper extremity, adult reconstructive, pediatrics, spine surgery and sports medicine. Poorly controlled diabetes negatively impacts bone, soft tissue, ligament and tendon healing. It is the complications of diabetes such as neuropathy, peripheral artery disease, and end stage renal disease which contributes to adverse outcomes. Well controlled diabetic patients without comorbidities have similar outcomes to patients without diabetes. Orthopaedic surgeons should utilize consultants who will assist in inpatient glycemic management as well as optimizing long term glycemic control.

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Section: General Issuesmentioning

confidence: 99%

Diabetes and its negative impact on outcomes in orthopaedic surgery

Wukich

2015

WJO

115

103

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“…Low intensity pulsed US have been used for diagnostic purposes for a long time and been shown to have a positive effect on bone regeneration and fracture healing. 5,12,37 Bone remodeling is a dynamic and continuous process. It has already been shown in different studies that NO modulates fracture healing.…”

Section: Discussionmentioning

confidence: 99%

Changes in NO, iNOS and eNOS Expression in MLO-Y4 Cells After Low-intensity Pulsed Ultrasound Treatment With or Without Shear Stress Exposure

Saini

McCormick

2010

Cel. Mol. Bioeng.

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Bone formation in vivo is stimulated by mechanical loads. The primary endogenous biomechanical stimulus at the cell level, which results from mechanical loading, is fluid shear stress. Pulsed ultrasound (US) also induces bone formation and accelerates fracture healing. To determine the combined effect of these mechanical stimuli, MLO-Y4 cells were exposed sequentially to US (1.5 MHz, 30 mW/cm 2 , 1 kHz pulse rate, 20% duty cycle) and fluid shear stress (SS) (19 dynes/cm 2 ) for a range of duration periods. Nitrite levels were measured which indirectly show the nitric oxide (NO) production from the cells. The amount of nitric oxide (NO) produced by cells exposed to combined US and SS treatments that consisted of equivalent exposure periods of 2.5, 5 and 10 min per treatment type, were respectively 0.7, 1.2 and 2.2 fold greater than the sum of the amounts of NO produced by cells exposed to lone US and shear stress treatments for the corresponding time periods (2.5, 5 and 10 min). Alone and in conjunction with mechanical stimuli, serum increases the NO production in the cells. 1400 W, a selective iNOS inhibitor, decreased by 33% the amount of NO produced by cells exposed sequentially to 10 min US and 10 min shear stress treatments. L-NAME, a non-selective inhibitor, completely inhibited NO production. Intermediate and long term experiments, where cells were exposed to US for 20 min and then to shear stress for 3 and 24 h, were also performed. For both durations nitrite levels were higher in the media of sequentially exposed cells than in the media of cells exposed to only one mechanical stimulus. In the long term, the rate of NO production decreased markedly. However, NO production remained significantly higher in the mechanically stimulated cells as compared to controls. In both the intermediate and long term experiments, US combined with SS to have a synergistic effect on eNOS mRNA levels and an additive effect on iNOS levels. These studies demonstrate that US and SS synergistically increase NO production in osteocyte-like cells and they suggest that it may be beneficial to use both exogenous US and endogenously derived SS to increase the formation of bone tissue.

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“…Some authors showed that, especially DM type 1, leads to a decreased proliferative activity of osteoblast progenitor cells and gene expression, an impairment in osteoblast function and osteoblast response to signaling cues, and an increased osteoclast proliferation, resulting in lower bone mineral density (BMD) and increased risk of fractures [3][4][5]. Moreover, it has been demonstrated that, after the occurrence of a fracture, the whole process of bone healing is impaired and delayed, which can result in nonunion fractures or pseudoarthrosis [3,6].…”

Section: Introductionmentioning

confidence: 98%

“…Some therapeutic interventions have been described by their osteogenic potential, including lowintensity therapeutic ultrasound [6,7], electromagnetic fields [8], and application of bone morphogenetic protein (BMP) [9]. In addition, a significant body of evidence has now accumulated demonstrating that photobiomodulation (PBM) also has a positive effect on bone tissue metabolism and on fracture consolidation [11][12][13][14][15][16].…”

Section: Introductionmentioning

confidence: 99%

Photobiomodulation and bone healing in diabetic rats: evaluation of bone response using a tibial defect experimental model

et al. 2015

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Diabetes mellitus (DM) leads to a delay in bone healing. Thus, some therapeutic approaches have been used to accelerate the process of bone repair such as photobiomodulation (PBM). Therefore, the present study aimed to evaluate the effects of PBM, in different fluences, in bone repair in an experimental model of tibial bone defects in diabetic rats. Sixty-four Wistar rats were submitted to a surgical procedure to perform bone defect and distributed in four groups: diabetic control group (DCG), diabetic laser group 30 J/cm(2) (L30), diabetic laser group 60 J/cm(2) (L60), and diabetic laser group 120 J/cm(2) (L120). A 808 nm Ga-Al-As (DMC Equipment, São Carlos, SP, Brazil) laser, 100 mW; 0.028 cm(2); 3.57 W/cm(2); 30, 60, and 120 J/cm(2); 0.84, 1.68, and 3.36 J; 8, 16, and 33 s was used. Animals were euthanized 15 and 30 days after the surgery. Histological, morphometric, immunohistochemistry, and biomechanical analyses were performed. In the histological and morphometric evaluation, all laser-treated groups showed a better histological pattern and a higher amount of newly formed bone compared to DCG. An intense RUNX2 immunoexpression was observed in the laser-treated groups, 15 days after the surgery. Receptor activator of nuclear factor κ-β ligand (RANK-L) immunohistochemistry analysis showed a significant decrease in the immunoreactivity for L30 and L120, 30 days after surgery. There was no statistical difference in the biomechanical analysis among the groups. In conclusion, PBM, in all fluences used, showed an osteogenic potential in bone healing of diabetic rats.

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The effects of low‐intensity pulsed ultrasound upon diabetic fracture healing

Cited by 51 publications

References 46 publications

Diabetes and its negative impact on outcomes in orthopaedic surgery

Diabetes and its negative impact on outcomes in orthopaedic surgery

Changes in NO, iNOS and eNOS Expression in MLO-Y4 Cells After Low-intensity Pulsed Ultrasound Treatment With or Without Shear Stress Exposure

Photobiomodulation and bone healing in diabetic rats: evaluation of bone response using a tibial defect experimental model

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